Characterisation of [3H]gabapentin binding to a novel site in rat brain: homogenate binding studies.

Abstract:

:The binding characteristics of [3H]gabapentin, the radiolabelled analogue of the novel anticonvulsant gabapentin (1-(aminomethyl)cyclohexaneacetic acid) were studied using purified synaptic plasma membranes prepared from rat cerebral cortex. In 10 mM HEPES buffer [3H]gabapentin bound to a single population of sites with high affinity (KD = 38 +/- 2.8 nM) with a maximum binding capacity of 4.6 +/- 0.4 pmol/mg protein, reaching equilibrium after 30 min at 20 degrees C. This novel site was unique to the central nervous system with little or no specific [3H]gabapentin being measurable in a range of peripheral tissues. Binding was potently inhibited by a range of gabapentin analogues and 3-alkyl substituted gamma-aminobutyric acid (GABA) derivates although GABA itself and the selective GABAB receptor ligand baclofen, were only weakly active. Gabapentin itself (IC50 = 80 nM) and 3-isobutyl GABA (IC50 = 80 nM) which also has anticonvulsant properties, showed the highest affinity for the binding site. Of a wide range of other pharmacologically active compounds only the polyamines spermine and spermidine influenced [3H]gabapentin binding, with both compounds producing a maximum of 50% inhibition of specific binding. Magnesium ions produced a similar pattern of inhibition but the effect of the polyamines and magnesium ions were not additive. The data provide evidence for the existence in brain of a novel binding site that may mediate the anticonvulsant effects of gabapentin and other potential anticonvulsant compounds.

journal_name

Eur J Pharmacol

authors

Suman-Chauhan N,Webdale L,Hill DR,Woodruff GN

doi

10.1016/0922-4106(93)90155-3

subject

Has Abstract

pub_date

1993-02-15 00:00:00

pages

293-301

issue

3

eissn

0014-2999

issn

1879-0712

journal_volume

244

pub_type

杂志文章
  • Further analyses of mechanisms underlying the antinociceptive effect of the triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene in mice.

    abstract::The present study investigated the mechanisms involved in the antinociception produced by the triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene (TTHL) in mice. TTHL administered by intra-gastric (i.g.) gavage inhibited glutamate-induced nociception with an ID(50) of 19.0 (13.2-27.5) mg/kg. This action started 60 min (in...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2010.11.028

    authors: Longhi-Balbinot DT,Martins DF,Lanznaster D,Silva MD,Facundo VA,Santos AR

    更新日期:2011-02-25 00:00:00

  • Potent inhibition of spontaneous rhythmic contraction by a novel beta 2-adrenoceptor agonist, HSR-81, in pregnant rat uterus.

    abstract::We examined the effect of HSR-81 ((-)-(R)-alpha-[(tert-butylamino)methyl]-2-chloro-4-hydroxybenzyl alcohol L-tartrate), a newly developed, potent and selective beta 2-adrenoceptor agonist, as well as ritodrine and isoproterenol, on the spontaneous rhythmic contraction in uteri isolated from late pregnant, middle pregn...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(96)00277-4

    authors: Ohashi T,Hashimoto S,Morikawa K,Kato H,Ito Y,Asano M,Azuma H

    更新日期:1996-07-04 00:00:00

  • Characterization of kappa opioid receptors in the rabbit ear artery.

    abstract::Quantitative characterization of the kappa opioid receptor in the rabbit ear artery was carried out using three kappa-selective agonist compounds, dynorphin-(1-13), U-69593 and ethylketocyclazocine. Kinetic analysis was performed using the antagonist, MR 2266. Two other in vitro preparations were studied for compariso...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(88)90542-0

    authors: Berzetei IP,Fong A,Yamamura HI,Duckles SP

    更新日期:1988-07-14 00:00:00

  • Telmisartan ameliorates experimental autoimmune myocarditis associated with inhibition of inflammation and oxidative stress.

    abstract::Excess cytokine produced by inflammatory stimuli contributes to the progression of myocardial damage in myocarditis. Angiotensin-II has been shown to play a pivotal role in the pathophysiology of various organs, especially the cardiovascular system. Some angiotensin II type 1 receptor antagonists are reported to inhib...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2010.10.081

    authors: Sukumaran V,Watanabe K,Veeraveedu PT,Ma M,Gurusamy N,Rajavel V,Suzuki K,Yamaguchi K,Kodama M,Aizawa Y

    更新日期:2011-02-10 00:00:00

  • Mediation of glutamatergic receptors and nitric oxide on striatal dopamine release evoked by anatoxin-a. An in vivo microdialysis study.

    abstract::In this work, the involvement of ionotropic glutamatergic receptors and nitric oxide on striatal dopamine release induced by anatoxin-a was investigated in conscious and freely-moving rats. To study the participation of glutamatergic receptors, the effects of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (A...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2006.07.044

    authors: Campos F,Alfonso M,Vidal L,Faro LR,Durán R

    更新日期:2006-10-24 00:00:00

  • Angiotensin II type 1 receptor blockade prevents decrease in adult stem-like cells in kidney after ureteral obstruction.

    abstract::Infusion of renal side population (SP) cells, enriched with adult stem-like cells, can ameliorate acute renal failure. We investigated the effects of an angiotensin II type 1 (AT(1)) receptor antagonist, valsartan on SP cell changes in renal injury by ureteral obstruction. Renal SP fraction was reduced by 38%, and the...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2007.07.032

    authors: Marumo T,Hishikawa K,Matsuzaki Y,Imai N,Takase O,Shimosawa T,Okano H,Fujita T

    更新日期:2007-11-14 00:00:00

  • Targeting different angiogenic pathways with combination of curcumin, leflunomide and perindopril inhibits diethylnitrosamine-induced hepatocellular carcinoma in mice.

    abstract::No effective chemopreventive agent has been approved against hepatocellular carcinoma (HCC) to date. Since HCC is one of the hypervascular solid tumors, blocking angiogenesis represents an intriguing approach to HCC chemoprevention. The aim of the current study was to examine the combined effect of the anti-angiogenic...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2013.11.022

    authors: Nasr M,Selima E,Hamed O,Kazem A

    更新日期:2014-01-15 00:00:00

  • Novel thienylacylhydrazone derivatives inhibit platelet aggregation through cyclic nucleotides modulation and thromboxane A2 synthesis inhibition.

    abstract::The aim of this study has been to investigate the antiplatelet activity of a new series of thienylacylhydrazone derivatives analogous to the lead compound LASSBio-294 ((2-thienylidene) 3,4-methylenedioxybenzoylhydrazine). The antiplatelet effect was investigated in rabbit and human platelet rich plasma stimulated by a...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2010.04.003

    authors: Brito FC,Kummerle AE,Lugnier C,Fraga CA,Barreiro EJ,Miranda AL

    更新日期:2010-07-25 00:00:00

  • Endothelium and cannabinoid receptor involvement in levcromakalim vasorelaxation.

    abstract::Levcromakalim was more potent at relaxing rat small mesenteric arteries with endothelium (EC50, 84+/-10 nM) than denuded vessels (EC50, 779+/-101 nM). The cannabinoid receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide hydrochloride; 1 microM...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0014-2999(97)01397-6

    authors: White R,Hiley CR

    更新日期:1997-11-27 00:00:00

  • Pharmacological characterization of AMPA-induced biting behaviour in mice.

    abstract::The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. It is well established that excitatory amino acids, aspartate and glutamate, are involved in the spinal transmission of nociceptive information and in the development of hyperalgesia. In the present study, intrathecal (i.t.) admi...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(96)00145-8

    authors: Brambilla A,Prudentino A,Grippa N,Borsini F

    更新日期:1996-06-03 00:00:00

  • Opposite effects of Bay k 8644 and nicardipine on the inhibitory effect of Ca2+ on rat myometrium.

    abstract::The effect of Ca2+ on the oxytocin-induced, sustained contraction of rat uterine muscle in Ca-free medium after prolonged incubation with 3 mM EGTA (Ca-free contraction) was investigated. A micromolar concentration of Ca2+ caused phasic contraction followed by relaxation while a submicromolar concentration caused rela...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(87)90286-x

    authors: Matsuo K,Uchida MK

    更新日期:1987-08-21 00:00:00

  • Pharmacological characterization of release-regulating serotonin autoreceptors in rat cerebellum.

    abstract::The release of [3H]5-hydroxytryptamine ([3H]5-HT) evoked by 15 mM KCl in superfused rat cerebellum synaptosomes was inhibited by 5-HT (pEC30 = 8.73). Methiothepin antagonized 5-HT (pA2 = 9.28); ketanserin, methysergide, cinanserin and spiperone were ineffective. The receptors involved were activated (pEC30 = 8.90) by ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(86)90065-8

    authors: Bonanno G,Maura G,Raiteri M

    更新日期:1986-07-31 00:00:00

  • Effects of NG-nitro-L-arginine on electrical and mechanical responses to stimulation of non-adrenergic, non-cholinergic inhibitory nerves in circular muscle of the rat gastric fundus.

    abstract::The effects of L-nitroarginine (L-NNA), an inhibitor of nitric oxide (NO) synthesis, on non-adrenergic, non-cholinergic inhibitory transmission in the circular smooth muscle of the rat gastric fundus were studied. The relaxation in response to nerve stimulation in the presence of guanethidine and atropine was depresse...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(93)90690-j

    authors: Shimamura K,Fujisawa A,Toda N,Sunano S

    更新日期:1993-01-26 00:00:00

  • Protective effect of [Pyr1]-apelin-13 on oxidative stress-induced apoptosis in hair cell-like cells derived from bone marrow mesenchymal stem cells.

    abstract::Oxidative stress plays an important role in auditory dysfunction. Exogenous cell therapy has brought new hopes for repairing mammalian inner ear hair cells. However, poor cell viability of transplanted cells under oxidative stress conditions has limited their therapeutic potential. The adipocytokine apelin-13 was isol...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2019.03.012

    authors: Niknazar S,Abbaszadeh HA,Peyvandi H,Rezaei O,Forooghirad H,Khoshsirat S,Peyvandi AA

    更新日期:2019-06-15 00:00:00

  • Endotoxin impairs the response of rat anococcygeus muscle to electrical field stimulation.

    abstract::Rat anococcygeus muscles were isolated 4 h after treatment with either E. coli endotoxin (20 mg kg-1 i.p.) or saline. The contractile responses of the muscle to electrical field stimulation, and to the alpha 1-adrenoceptor agonist cirazoline were impaired by endotoxin treatment. Inhibition of the L-arginine pathway wi...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(91)90285-x

    authors: Guc MO,Furman BL,Parratt JR

    更新日期:1991-09-24 00:00:00

  • Curcumol exhibits anti-inflammatory properties by interfering with the JNK-mediated AP-1 pathway in lipopolysaccharide-activated RAW264.7 cells.

    abstract::Curcumol is one of the major components of the essential oil of Rhizoma Curcumae, a common traditional Chinese medicine with anti-inflammatory properties. However, the anti-inflammatory activity and the underlying molecular mechanisms of this compound remain unclear. In the present study, the anti-inflammation effect ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2013.11.007

    authors: Chen X,Zong C,Gao Y,Cai R,Fang L,Lu J,Liu F,Qi Y

    更新日期:2014-01-15 00:00:00

  • Oxyntomodulin and its (19-37) and (30-37) fragments inhibit histamine-stimulated gastric acid secretion in the conscious rat.

    abstract::Oxyntomodulin, a hormone released from jejuno-ileum and composed of the glucagon sequence extended by a C-terminal octapeptide displays original tissue specificity for the gastric mucosa. The aim of this study was to compare the effect of oxyntomodulin on histamine (0.4 mg/kg per h)-stimulated gastric acid secretion i...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(91)90720-b

    authors: Carles-Bonnet C,Jarrousse C,Niel H,Martinez J,Bataille D

    更新日期:1991-10-15 00:00:00

  • Methoctramine, a selective M2 alpha muscarinic receptor antagonist, does not inhibit carbachol-induced drinking in the rat.

    abstract::Methoctramine, a selective M2 alpha muscarinic receptor antagonist, was examined for its ability to inhibit carbachol-induced drinking in the rat. Intracerebroventricularly (i.c.v.) administered methoctramine was devoid of activity up to a dose of 100 nmol/rat, whereas higher doses were toxic under our experimental co...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(89)90213-6

    authors: Massi M,Polidori C,Melchiorre C

    更新日期:1989-04-25 00:00:00

  • Substance P suppresses stress-induced eating.

    abstract::Parenterally administered substance P suppressed stress-induced eating (resulting from mild tail pinch) in a dose-related manner, whereas at similar or higher doses of substance P starvation-induced eating was uneffected. This specific effect of substance P on stress-induced eating is possibly associated with alterati...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(80)90514-2

    authors: Morley JE,Levine AS

    更新日期:1980-10-17 00:00:00

  • The enantiomers of the D-2 dopamine receptor agonist N-0437 discriminate between pre- and postsynaptic dopamine receptors.

    abstract::The (+) and (-) enantiomers of the substituted 2-aminotetralin, N-0437 were evaluated in vivo for their dopaminergic activity, using biochemical as well as behavioural models. In presynaptic models, i.e. antagonism of gamma-butyrolactone-induced dihydroxyphenylalanine elevations and the induction of hypomotility, both...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(88)90309-3

    authors: Van der Weide J,Tendijck ME,Tepper PG,De Vries JB,Dubocovich ML,Horn AS

    更新日期:1988-02-09 00:00:00

  • Capsazepine inhibits low pH- and lactic acid-evoked release of calcitonin gene-related peptide from sensory nerves in guinea-pig heart.

    abstract::In the isolated perfused guinea-pig heart low-pH buffer (pH 5), lactic acid (5 mM), capsaicin (10(-7) M) and nicotine (10(-4) M) all evoked a clear-cut release of calcitonin gene-related peptide (CGRP) from sensory nerves. Incubation with the proposed capsaicin receptor antagonist, capsazepine (10(-5) M), significantl...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(92)90792-3

    authors: Franco-Cereceda A,Lundberg JM

    更新日期:1992-10-06 00:00:00

  • MDMA- and p-chlorophenylalanine-induced reduction in 5-HT concentrations: effects on serotonin transporter densities.

    abstract::Low levels of serotonin may reduce the density of the serotonin transporter (SERT) by either increasing trafficking or reducing synthesis; a "neuroadaptive response". To determine whether 3,4-methylenedioxymethamphetamine (MDMA)-induced reductions in SERT density could be related to such a mechanism, p-chlorophenylala...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章,收录出版

    doi:10.1016/s0014-2999(02)02420-2

    authors: Boot BP,Mechan AO,McCann UD,Ricaurte GA

    更新日期:2002-10-25 00:00:00

  • Pharmacology of ectonucleotidases: relevance for the treatment of cardiovascular disorders.

    abstract::ATP and other extracellular nucleotides have diverse and potent effects in different organs. Evidence indicates that extracellular nucleotides and nucleosides deliver crucial signals by acting upon a wide variety of purinergic receptors, which include 19 members separated in three families. Purinergic receptors encomp...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2012.09.003

    authors: Mathieu P

    更新日期:2012-12-05 00:00:00

  • Muscarinic receptor agonists decrease cocaine self-administration rates in drug-naive mice.

    abstract::(5R,6R)-6-(3-Propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[ 3.2.1]octane (PTAC) is a selective muscarinic receptor ligand. The compound exhibits high affinity for central muscarinic receptors with partial agonist mode of action at muscarinic M(2) and M(4) and antagonist mode of action at muscarinic M(1), M(3) and M(5...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0014-2999(00)00442-8

    authors: Rasmussen T,Sauerberg P,Nielsen EB,Swedberg MD,Thomsen C,Sheardown MJ,Jeppesen L,Calligaro DO,DeLapp NW,Whitesitt C,Ward JS,Shannon HE,Bymaster FP,Fink-Jensen A

    更新日期:2000-08-25 00:00:00

  • Acamprosate and alcohol: II. Effects on alcohol withdrawal in the rat.

    abstract::The suppressing effect of acamprosate (calcium-acetyl homotaurinate) on alcohol drinking is well established; however, little is known about its effects upon the alcohol-induced withdrawal syndrome. Male Wistar rats received as a sole drinking fluid a 20% (v/v) alcohol solution for one week. Animals consumed on averag...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(96)00175-6

    authors: Spanagel R,Putzke J,Stefferl A,Schöbitz B,Zieglgänsberger W

    更新日期:1996-06-03 00:00:00

  • Comparison of pharmacological activities of Neuropeptide FF1 and Neuropeptide FF2 receptor agonists.

    abstract::The pharmacological effects of Neuropeptide FF (NPFF) analogs exhibiting different selectivities towards Neuropeptide FF1 (NPFF1) and Neuropeptide FF2 (NPFF2) receptors were investigated after supraspinal administration in mice. Injected into the third ventricle, VPNLPQRF-NH2, which is selective for Neuropeptide FF1 r...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2004.12.002

    authors: Quelven I,Roussin A,Zajac JM

    更新日期:2005-01-31 00:00:00

  • The effect of catecholamine depletion on the bradykinin-induced relaxation of isolated smooth muscle.

    abstract::The effect of depletion of catecholamines by tyramine or reserpine on the bradykinin-induced relaxation of the rat duodenum aan rabbit ileum was the object of this study. The relaxation was not affected by catecholamine depletion due to repeated addition of tyramine to the isolated organs from either normal or reserpi...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(75)90148-x

    authors: Ufkes JG,Van der Meer C

    更新日期:1975-08-01 00:00:00

  • The potent and selective dopamine D1 receptor agonist A-77636 increases cortical and hippocampal acetylcholine release in the rat.

    abstract::The effects of systemic administration of the full dopamine D1 receptor agonist A-77636 on acetylcholine release in rat frontal cortex and hippocampus were studied using in vivo microdialysis. Administration of A-77636 (4 mumol/kg s.c.) greatly (> 230%) increased both cortical and hippocampal acetylcholine release for...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(94)90013-2

    authors: Acquas E,Day JC,Fibiger HC

    更新日期:1994-07-21 00:00:00

  • Serotonin receptors in hippocampus and frontal cortex.

    abstract::The inhibition by various serotonin agonists and antagonists of the binding of 3 nM 3H-d-LSD, 1.7 nM 3H-serotonin and 0.22 nM 3H-spiperone to homogenates of calf hippocampus and frontal cortex was studied. The 50% inhibitory concentration (IC50) for these drugs versus 3H-d-LSD binding had similar values to and correla...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(80)90141-7

    authors: Seeman P,Westman K,Coscina D,Warsh JJ

    更新日期:1980-08-29 00:00:00

  • Biphasic effect of a kappa-opioid receptor agonist on plasma oxytocin levels in rats.

    abstract::The effect of the kappa-opioid receptor agonist, bremazocine, on plasma oxytocin levels in rats was measured by a sensitive radioimmunoassay. Initially, a decrease in plasma oxytocin levels was seen 30 min after injection. This was in accordance with the bremazocine inhibition of oxytocin release after submaximal elec...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(89)90681-x

    authors: Grell S,Fjalland B,Christensen JD

    更新日期:1989-07-04 00:00:00